The present invention relates, in general, to a method and apparatus for analysis of chemical species separated by differences in flow rate through a porous medium, and, more particularly, to a method and apparatus for analysis of such species through optical absorption, reflection, refraction or fluorescence simultaneously in multiple micron-scale optical channels. The invention further relates to a microfabricated porous medium for such channels.
Optical systems for use in chemical analysis are well known, and the use of such systems in electrophoretic DNA sequencing is a particularly important application because of the intense interest in the sequencing of the human genome. This is a multiyear, multibillion dollar project which is directed to improving, if not revolutionizing, the ability to diagnose and treat illness.
Significant progress is being made in this field, and commercial optical systems are now available which are capable of sequencing DNA by gel electrophoresis of fluorescently labeled DNA fragments.
Because DNA sequencing is a highly complex procedure which requires a great deal of time and involves high cost, a considerable amount of research is being done into techniques and devices for reducing the time required for such sequencing, with one technique including the parallel reading of fluorescence from multiple capillaries. However, problems still remain in processing the DNA, in supplying it to the capillaries, in causing the DNA to pass through the capillaries, and in optically reading out the results, for currently available systems are relatively large, are expensive, and, although capable of operating faster than previous systems, still require very long time periods to sequence DNA fractions. Thus, the time required to sequence the three billion base pairs which comprise the human genome is still measured in years, and, there is an urgent need for an improved optical system for carrying out such procedures. Such an improved system would also have application in the analysis of other chemical species, particularly where the species are separated by differences in flow rate through a porous medium.
In electrophoretic analysis, chemical species are separated by an electric field which produces varying flow rates, and the separated products may then be detected optically. In typical DNA sequencing applications, the DNA fragments to be analyzed are added to a gel material which carries the fragments through electrophoresis channels. Such gels create problems, however, since it is difficult to fill narrow capillaries with the gel material, thereby increasing the time required and the expense of carrying out the sequencing process. Efforts have been made to develop an artificial gel material in the form of a porous medium, but the dimensions of such structures have been limited to those obtainable by photolithography. In addition, the production of artificial gel structures by such a process is too expensive for practical use. Thus, there is a need for an artificial gel structure which can be formed by processes that are easily carried out over large areas and which can be fabricated in inexpensive materials. Such a gel material would find wide use in a miniaturized, compact, and proportionately less expensive systems for chemical analysis.